Variant chr15-90970444-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003981.4(PRC1):c.1532A>G(p.Tyr511Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 1,613,012 control chromosomes in the GnomAD database, including 4,426 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.052 ( 293 hom., cov: 31)

Exomes 𝑓: 0.069 ( 4133 hom. )

Consequence

PRC1
NM_003981.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.585

Variant links:

Genes affected

PRC1 (HGNC:9341): (protein regulator of cytokinesis 1) This gene encodes a protein that is involved in cytokinesis. The protein is present at high levels during the S and G2/M phases of mitosis but its levels drop dramatically when the cell exits mitosis and enters the G1 phase. It is located in the nucleus during interphase, becomes associated with mitotic spindles in a highly dynamic manner during mitosis, and localizes to the cell mid-body during cytokinesis. This protein has been shown to be a substrate of several cyclin-dependent kinases (CDKs). It is necessary for polarizing parallel microtubules and concentrating the factors responsible for contractile ring assembly. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

PRC1 links:

PRC1-AS1 (HGNC:48587): (PRC1 antisense RNA 1)

PRC1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016720891).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRC1	NM_003981.4 linkuse as main transcript	c.1532A>G	p.Tyr511Cys	missense_variant	12/15	ENST00000394249.8
PRC1-AS1	NR_051984.1 linkuse as main transcript	n.310+3766T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRC1	ENST00000394249.8 linkuse as main transcript	c.1532A>G	p.Tyr511Cys	missense_variant	12/15	1	NM_003981.4		O43663-1
PRC1-AS1	ENST00000554388.2 linkuse as main transcript	n.339+3766T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0518

AC:

7872

AN:

152078

Hom.:

296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.0375

Gnomad ASJ

AF:

0.0764

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.0724

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0712

Gnomad OTH

AF:

0.0532

GnomAD3 exomes

AF:

0.0646

AC:

16228

AN:

251372

Hom.:

807

AF XY:

0.0710

AC XY:

9640

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0102

Gnomad AMR exome

AF:

0.0252

Gnomad ASJ exome

AF:

0.0751

Gnomad EAS exome

AF:

0.00190

Gnomad SAS exome

AF:

0.155

Gnomad FIN exome

AF:

0.0705

Gnomad NFE exome

AF:

0.0680

Gnomad OTH exome

AF:

0.0648

GnomAD4 exome

AF:

0.0692

AC:

101055

AN:

1460816

Hom.:

4133

Cov.:

AF XY:

0.0718

AC XY:

52214

AN XY:

726746

show subpopulations

Gnomad4 AFR exome

AF:

0.00992

Gnomad4 AMR exome

AF:

0.0274

Gnomad4 ASJ exome

AF:

0.0716

Gnomad4 EAS exome

AF:

0.00197

Gnomad4 SAS exome

AF:

0.151

Gnomad4 FIN exome

AF:

0.0692

Gnomad4 NFE exome

AF:

0.0689

Gnomad4 OTH exome

AF:

0.0667

GnomAD4 genome

AF:

0.0517

AC:

7864

AN:

152196

Hom.:

293

Cov.:

AF XY:

0.0519

AC XY:

3865

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0113

Gnomad4 AMR

AF:

0.0374

Gnomad4 ASJ

AF:

0.0764

Gnomad4 EAS

AF:

0.00328

Gnomad4 SAS

AF:

0.145

Gnomad4 FIN

AF:

0.0724

Gnomad4 NFE

AF:

0.0712

Gnomad4 OTH

AF:

0.0526

Alfa

AF:

0.0675

Hom.:

771

Bravo

AF:

0.0453

TwinsUK

AF:

0.0715

AC:

265

ALSPAC

AF:

0.0711

AC:

274

ESP6500AA

AF:

0.0152

AC:

ESP6500EA

AF:

0.0735

AC:

632

ExAC

AF:

0.0658

AC:

7989

Asia WGS

AF:

0.0790

AC:

275

AN:

3478

EpiCase

AF:

0.0749

EpiControl

AF:

0.0675

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Familial cancer of breast

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Research Lab, National Institute of Public Health

Feb 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.3

DANN

Benign

0.51

DEOGEN2

Benign

0.053

T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.94

D;D;D

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.40

N;N;.

MutationTaster

Benign

0.63

D;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.53

N;N;N

REVEL

Benign

0.055

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.24

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.042

MPC

0.093

ClinPred

0.0054

GERP RS

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over